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Uracil
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<h2 id="properties">Properties</h2> <p>In RNA, uracil <a href="/facts/Base_pair/xmPpPQ9W">base-pairs</a> with adenine and replaces thymine during DNA transcription. <a href="/facts/Methylation/EvDMWVW5">Methylation</a> of uracil produces thymine.<a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a> In DNA, the evolutionary substitution of thymine for uracil may have increased DNA stability and improved the efficiency of <a href="/facts/DNA_replication/wrU6RuR3">DNA replication</a> (discussed below). Uracil pairs with adenine through <a href="/facts/Hydrogen_bonding/85V86IIg">hydrogen bonding</a>. When <a href="/facts/Base_pairing/xmPpPQ9W">base pairing</a> with adenine, uracil acts as both a <a href="/facts/Hydrogen_bond/85V86IIg">hydrogen bond</a> acceptor and a hydrogen bond donor. In RNA, uracil binds with a <a href="/facts/Ribose/VFKYCzPV">ribose</a> sugar to form the <a href="/facts/Ribonucleoside/8lAokLM4">ribonucleoside</a> <a href="/facts/Uridine/HXS43chN">uridine</a>. When a <a href="/facts/Phosphate/FDGVCxUG">phosphate</a> attaches to uridine, uridine 5′-monophosphate is produced.<a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a> </p><p>Uracil undergoes amide-imidic acid tautomeric shifts because any nuclear instability the molecule may have from the lack of formal <a href="/facts/Aromaticity/wK0DzRY6">aromaticity</a> is compensated by the cyclic-amidic stability.<a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a> The amide <a href="/facts/Tautomer/ucdXGP9C">tautomer</a> is referred to as the <a href="/facts/Lactam/2VVAzXVX">lactam</a> structure, while the imidic acid tautomer is referred to as the <a href="/facts/Lactim/2VVAzXVX">lactim</a> structure. These tautomeric forms are predominant at <a href="/facts/PH/RnSv8D7y">pH</a> 7. The lactam structure is the most common form of uracil. </p> <p>Uracil also recycles itself to form nucleotides by undergoing a series of phosphoribosyltransferase reactions.<a class="footnote-ref" id="fnref:13" href="#fn:13"><sup>13</sup></a> Degradation of uracil produces the substrates <a href="/facts/%25CE%2592-alanine/9RHTHPPQ">β-alanine</a>, <a href="/facts/Carbon_dioxide/xGzpppEp">carbon dioxide</a>, and <a href="/facts/Ammonia/MtLtJFtz">ammonia</a>.<a class="footnote-ref" id="fnref:14" href="#fn:14"><sup>14</sup></a> </p> C4H4N2O2→ H3NCH2CH2COO− + NH+4 + CO2 <p>Oxidative degradation of uracil produces urea and maleic acid in the presence of <a href="/facts/Hydrogen_peroxide/vju6HBIc">H2O2</a> and <a href="/facts/Iron/QK1JYy8E">Fe</a>2+ or in the presence of diatomic <a href="/facts/Oxygen/acyn6o8r">oxygen</a> and Fe2+. </p><p>Uracil is a <a href="/facts/Weak_acid/vJ4rj6Lu">weak acid</a>. The first site of <a href="/facts/Ionization/W13Ceavd">ionization</a> of uracil is not known.<a class="footnote-ref" id="fnref:15" href="#fn:15"><sup>15</sup></a> The negative charge is placed on the oxygen anion and produces a <a href="/facts/Acid_dissociation_constant/t4YyRtKC">p<i>K</i>a</a> of less than or equal to 12. The basic p<i>K</i>a = −3.4, while the acidic p<i>K</i>a = 9.389. In the gas phase, uracil has four sites that are more acidic than water.<a class="footnote-ref" id="fnref:16" href="#fn:16"><sup>16</sup></a> </p> <h3>In DNA</h3> <p>Uracil is rarely found in DNA, and this may have been an evolutionary change to increase genetic stability. This is because cytosine can deaminate spontaneously to produce uracil through hydrolytic deamination. Therefore, if there were an organism that used uracil in its DNA, the deamination of cytosine (which undergoes base pairing with guanine) would lead to formation of uracil (which would base pair with adenine) during DNA synthesis. <a href="/facts/Uracil-DNA_glycosylase/EG3NgsbC">Uracil-DNA glycosylase</a> excises uracil bases from double-stranded DNA. This enzyme would therefore recognize and cut out both types of uracil – the one incorporated naturally, and the one formed due to cytosine deamination, which would trigger unnecessary and inappropriate repair processes.<a class="footnote-ref" id="fnref:17" href="#fn:17"><sup>17</sup></a> </p><p>This problem is believed to have been solved in terms of evolution, that is by "tagging" (methylating) uracil. Methylated uracil is identical to thymine. Hence the hypothesis that, over time, thymine became standard in DNA instead of uracil. So cells continue to use uracil in RNA, and not in DNA, because RNA is shorter-lived than DNA, and any potential uracil-related errors do not lead to lasting damage. Apparently, either there was no evolutionary pressure to replace uracil in RNA with the more complex thymine, or uracil has some chemical property that is useful in RNA, which thymine lacks. Uracil-containing DNA still exists, for example in: </p> <ul><li>DNA of several <a href="/facts/Phage/L2Ll0T3q">phages</a><a class="footnote-ref" id="fnref:18" href="#fn:18"><sup>18</sup></a></li> <li><a href="/facts/Endopterygote/8ErqpgDW">Endopterygote</a> development</li> <li>Hypermutations during the synthesis of vertebrate antibodies.</li></ul> <h2 id="synthesis">Synthesis</h2> <h3>Biological</h3> <p class="note">See also: <a href="/facts/Pyrimidine_metabolism/tItapHSg">Pyrimidine metabolism</a></p> <p>Organisms synthesize uracil, in the form of <a href="/facts/Uridine_monophosphate/TkB63ofX">uridine monophosphate</a> (UMP), by decarboxylating <a href="/facts/Orotidine_5%2527-monophosphate/UumglNKF">orotidine 5'-monophosphate</a> (orotidylic acid). In humans this decarboxylation is achieved by the enzyme <a href="/facts/Uridine_monophosphate_synthase/ylk4Yu68">UMP synthase</a>. In contrast to the purine nucleotides, the pyrimidine ring (orotidylic acid) that leads uracil is synthesized first and then linked to <a href="/facts/Ribose_phosphate/gMzSE2e1">ribose phosphate</a>, forming UMP.<a class="footnote-ref" id="fnref:19" href="#fn:19"><sup>19</sup></a> </p> <h3>Laboratory</h3> <p>There are many laboratory <a href="/facts/Chemical_synthesis/3KXsVVwC">synthesis</a> of uracil available. The first reaction is the simplest of the syntheses, by adding water to <a href="/facts/Cytosine/JW20j33u">cytosine</a> to produce uracil and <a href="/facts/Ammonia/MtLtJFtz">ammonia</a>:<a class="footnote-ref" id="fnref:20" href="#fn:20"><sup>20</sup></a> </p> C4H5N3O + H2O → C4H4N2O2 + NH3 <p>The most common way to synthesize uracil is by the <a href="/facts/Condensation/yvmkI08A">condensation</a> of <a href="/facts/Malic_acid/mSbExe77">malic acid</a> with urea in <a href="/facts/Fuming_sulfuric_acid/oyT7XMod">fuming sulfuric acid</a>:<a class="footnote-ref" id="fnref:21" href="#fn:21"><sup>21</sup></a> </p> C4H4O4 + NH2CONH2 → C4H4N2O2 + 2 H2O + CO <p>Uracil can also be synthesized by a double decomposition of <a href="/facts/2-Thiouracil/zq6NxHLb">thiouracil</a> in aqueous <a href="/facts/Chloroacetic_acid/aNNF8203">chloroacetic acid</a>.<a class="footnote-ref" id="fnref:22" href="#fn:22"><sup>22</sup></a> </p><p><a href="/facts/Photodehydrogenation/vwFAAqzp">Photodehydrogenation</a> of 5,6-diuracil, which is synthesized by beta-<a href="/facts/Alanine/fphQEdSc">alanine</a> reacting with <a href="/facts/Urea/6j84AoCG">urea</a>, produces uracil.<a class="footnote-ref" id="fnref:23" href="#fn:23"><sup>23</sup></a> </p> <h3>Prebiotic</h3> <p>In 2009, <a href="/facts/NASA/TIMCV0yV">NASA</a> scientists reported having produced uracil from <a href="/facts/Pyrimidine/uFRSB8Cq">pyrimidine</a> and water ice by exposing it to <a href="/facts/Ultraviolet_light/kncBUqn5">ultraviolet light</a> under space-like conditions.<a class="footnote-ref" id="fnref:24" href="#fn:24"><sup>24</sup></a> This suggests a possible natural original source for uracil.<a class="footnote-ref" id="fnref:25" href="#fn:25"><sup>25</sup></a> In 2014, NASA scientists reported that additional complex <a href="/facts/DNA/nB89Iauz">DNA</a> and <a href="/facts/RNA/HxPeNfNj">RNA</a> <a href="/facts/Organic_compound/gqCNaN45">organic compounds</a> of <a href="/facts/Life/DNw7NUId">life</a>, including uracil, <a href="/facts/Cytosine/JW20j33u">cytosine</a> and <a href="/facts/Thymine/A5C8MnLN">thymine</a>, have been formed in the laboratory under <a href="/facts/Outer_space/R3LRKyFs">outer space</a> conditions, starting with ice, <a href="/facts/Pyrimidine/uFRSB8Cq">pyrimidine</a>, ammonia, and methanol, which are compounds found in astrophysical environments.<a class="footnote-ref" id="fnref:26" href="#fn:26"><sup>26</sup></a> Pyrimidine, like <a href="/facts/Polycyclic_aromatic_hydrocarbons/K52xSfNC">polycyclic aromatic hydrocarbons</a> (PAHs), a carbon-rich chemical found in the <a href="/facts/Universe/XbfpnDmM">Universe</a>, may have been formed in <a href="/facts/Red_giant/lla6Bsvy">red giants</a> or in <a href="/facts/Cosmic_dust/Uy6hlL29">interstellar dust</a> and gas clouds.<a class="footnote-ref" id="fnref:27" href="#fn:27"><sup>27</sup></a> </p><p>Based on 12C/13C <a href="/facts/Isotopic_ratio/dGjaAwc9">isotopic ratios</a> of <a href="/facts/Organic_compounds/gqCNaN45">organic compounds</a> found in the <a href="/facts/Murchison_meteorite/5czfCWCu">Murchison meteorite</a>, it is believed that uracil, <a href="/facts/Xanthine/3ARA2QCg">xanthine</a>, and related molecules can also be formed extraterrestrially.<a class="footnote-ref" id="fnref:28" href="#fn:28"><sup>28</sup></a> Data from the <a href="/facts/Cassini_mission/PWknrDeY">Cassini mission</a>, orbiting in the <a href="/facts/Saturn/D54LcGJ9">Saturn</a> system, suggests that uracil is present in the surface of the moon <a href="/facts/Titan_(moon)/lg0l9PCH">Titan</a>.<a class="footnote-ref" id="fnref:29" href="#fn:29"><sup>29</sup></a> In 2023, uracil was observed in a sample from <a href="/facts/162173_Ryugu/I3RA3ITC">162173 Ryugu</a>, a <a href="/facts/Near-Earth_asteroid/UwnPRnSN">near-Earth asteroid</a>, with no exposure to Earth's biosphere, giving further evidence for synthesis in space.<a class="footnote-ref" id="fnref:30" href="#fn:30"><sup>30</sup></a> </p> <h2 id="reactions">Reactions</h2> <p>Uracil readily undergoes regular reactions including <a href="/facts/Oxidation/Pyd5RVcj">oxidation</a>, <a href="/facts/Nitration/VnszL09H">nitration</a>, and <a href="/facts/Alkylation/1rd5SNbt">alkylation</a>. While in the presence of <a href="/facts/Phenol/ACJs5NIU">phenol</a> (PhOH) and <a href="/facts/Sodium_hypochlorite/sp99uHHQ">sodium hypochlorite</a> (NaOCl), uracil can be visualized in <a href="/facts/Ultraviolet_light/kncBUqn5">ultraviolet light</a>.<a class="footnote-ref" id="fnref:31" href="#fn:31"><sup>31</sup></a> Uracil also has the capability to react with elemental <a href="/facts/Halogen/YeFgWHeA">halogens</a> because of the presence of more than one strongly electron donating group.<a class="footnote-ref" id="fnref:32" href="#fn:32"><sup>32</sup></a> </p><p>Uracil readily undergoes addition to <a href="/facts/Ribose/VFKYCzPV">ribose</a> <a href="/facts/Sugar/jb5KXRHT">sugars</a> and <a href="/facts/Phosphate/FDGVCxUG">phosphates</a> to partake in synthesis and further reactions in the body. Uracil becomes <a href="/facts/Uridine/HXS43chN">uridine</a>, <a href="/facts/Uridine_monophosphate/TkB63ofX">uridine monophosphate</a> (UMP), <a href="/facts/Uridine_diphosphate/QjoF1ssX">uridine diphosphate</a> (UDP), <a href="/facts/Uridine_triphosphate/5Dw5JaG2">uridine triphosphate</a> (UTP), and <a href="/facts/Uridine_diphosphate_glucose/xwQC6bEN">uridine diphosphate glucose</a> (UDP-glucose). Each one of these molecules is synthesized in the body and has specific functions. </p><p>When uracil reacts with anhydrous <a href="/facts/Hydrazine/G7P5ITzU">hydrazine</a>, a first-order kinetic reaction occurs and the uracil ring opens up.<a class="footnote-ref" id="fnref:33" href="#fn:33"><sup>33</sup></a> If the <a href="/facts/PH/RnSv8D7y">pH</a> of the reaction increases to > 10.5, the uracil anion forms, making the reaction go much more slowly. The same slowing of the reaction occurs if the pH decreases, because of the protonation of the hydrazine.<a class="footnote-ref" id="fnref:34" href="#fn:34"><sup>34</sup></a> The reactivity of uracil remains unchanged, even if the temperature changes.<a class="footnote-ref" id="fnref:35" href="#fn:35"><sup>35</sup></a> </p> <h2 id="uses">Uses</h2> <p>Uracil's use in the body is to help carry out the synthesis of many enzymes necessary for cell function through bonding with riboses and phosphates.<a class="footnote-ref" id="fnref:36" href="#fn:36"><sup>36</sup></a> Uracil serves as <a href="/facts/Allosteric/alMRuyt9">allosteric</a> regulator and <a href="/facts/Coenzyme/AGo0PCUU">coenzyme</a> for reactions in animals and in plants.<a class="footnote-ref" id="fnref:37" href="#fn:37"><sup>37</sup></a> UMP controls the activity of <a href="/facts/Carbamoyl_phosphate_synthetase/XnRrFoMR">carbamoyl phosphate synthetase</a> and <a href="/facts/Aspartate_transcarbamoylase/b2NCoTNh">aspartate transcarbamoylase</a> in plants, while UDP and UTP regulate CPSase II activity in <a href="/facts/Animal/4b8J33nd">animals</a>. UDP-glucose regulates the conversion of <a href="/facts/Glucose/oUSkoLCD">glucose</a> to <a href="/facts/Galactose/sh2hEFpC">galactose</a> in the <a href="/facts/Liver/Rtp4Fk2b">liver</a> and other tissues in the process of <a href="/facts/Carbohydrate_metabolism/h2WvuF14">carbohydrate metabolism</a>.<a class="footnote-ref" id="fnref:38" href="#fn:38"><sup>38</sup></a> Uracil is also involved in the <a href="/facts/Biosynthesis/aFk7Tk7f">biosynthesis</a> of <a href="/facts/Polysaccharides/lqXq2cJU">polysaccharides</a> and the transportation of sugars containing <a href="/facts/Aldehydes/xSIRkW03">aldehydes</a>.<a class="footnote-ref" id="fnref:39" href="#fn:39"><sup>39</sup></a> Uracil is important for the detoxification of many <a href="/facts/Carcinogen/soH8Y9CE">carcinogens</a>, for instance those found in tobacco smoke.<a class="footnote-ref" id="fnref:40" href="#fn:40"><sup>40</sup></a> Uracil is also required to detoxify many drugs such as cannabinoids (THC)<a class="footnote-ref" id="fnref:41" href="#fn:41"><sup>41</sup></a> and morphine (opioids).<a class="footnote-ref" id="fnref:42" href="#fn:42"><sup>42</sup></a> It can also slightly increase the risk for cancer in unusual cases in which the body is extremely deficient in <a href="/facts/Folate/8Eb7An6D">folate</a>.<a class="footnote-ref" id="fnref:43" href="#fn:43"><sup>43</sup></a> The deficiency in folate leads to increased ratio of <a href="/facts/Deoxyuridine_monophosphate/5oHCvTSx">deoxyuridine monophosphates</a> (dUMP)/<a href="/facts/Deoxythymidine_monophosphate/t2wx1hBG">deoxythymidine monophosphates</a> (dTMP) and uracil misincorporation into DNA and eventually low production of DNA.<a class="footnote-ref" id="fnref:44" href="#fn:44"><sup>44</sup></a> </p><p>Uracil can be used for <a href="/facts/Drug_delivery/vDfboXeT">drug delivery</a> and as a <a href="/facts/Pharmaceutical/h9mhwWP2">pharmaceutical</a>. When elemental <a href="/facts/Fluorine/YUV0Fb8m">fluorine</a> reacts with uracil, they produce <a href="/facts/5-fluorouracil/6xH4uUaf">5-fluorouracil</a>. 5-Fluorouracil is an anticancer drug (<a href="/facts/Antimetabolite/NICtB9BU">antimetabolite</a>) used to masquerade as uracil during the nucleic acid replication process.<a class="footnote-ref" id="fnref:45" href="#fn:45"><sup>45</sup></a> Because 5-fluorouracil is similar in shape to, but does not undergo the same chemistry as, uracil, the drug inhibits <a href="/facts/RNA/HxPeNfNj">RNA</a> transcription enzymes, thereby blocking RNA synthesis and stopping the growth of cancerous cells.<a class="footnote-ref" id="fnref:46" href="#fn:46"><sup>46</sup></a> Uracil can also be used in the synthesis of caffeine.<a class="footnote-ref" id="fnref:47" href="#fn:47"><sup>47</sup></a> Uracil has also shown potential as a HIV viral capsid inhibitor.<a class="footnote-ref" id="fnref:48" href="#fn:48"><sup>48</sup></a> Uracil derivatives have antiviral, anti-tubercular and anti-leishmanial activity.<a class="footnote-ref" id="fnref:49" href="#fn:49"><sup>49</sup></a><a class="footnote-ref" id="fnref:50" href="#fn:50"><sup>50</sup></a><a class="footnote-ref" id="fnref:51" href="#fn:51"><sup>51</sup></a> </p><p>Uracil can be used to determine <a href="/facts/Microbial/pysJYcE2">microbial</a> contamination of <a href="/facts/Tomato/3d5Xsqw7">tomatoes</a>. The presence of uracil indicates <a href="/facts/Lactic_acid/BsVRFx7s">lactic acid</a> <a href="/facts/Bacteria/wC8xSCsU">bacteria</a> contamination of the fruit.<a class="footnote-ref" id="fnref:52" href="#fn:52"><sup>52</sup></a> Uracil derivatives containing a <a href="/facts/Diazine/zkPYwuJw">diazine</a> ring are used in <a href="/facts/Pesticide/Uhf4KnwJ">pesticides</a>.<a class="footnote-ref" id="fnref:53" href="#fn:53"><sup>53</sup></a> Uracil derivatives are more often used as antiphotosynthetic <a href="/facts/Herbicide/FN93bvrk">herbicides</a>, destroying weeds in <a href="/facts/Cotton/efXRcjbn">cotton</a>, <a href="/facts/Sugar_beet/Rzcof5lb">sugar beet</a>, <a href="/facts/Turnip/dIkKUdIG">turnips</a>, <a href="/facts/Soybean/reNwxvo2">soya</a>, <a href="/facts/Pea/hlndxpId">peas</a>, <a href="/facts/Sunflower/KIv0oR5w">sunflower</a> crops, <a href="/facts/Vineyard/HCEJJcA2">vineyards</a>, <a href="/facts/Berry/PW8Tvdgu">berry</a> plantations, and <a href="/facts/Orchard/N7jv0Wrz">orchards</a>.<a class="footnote-ref" id="fnref:54" href="#fn:54"><sup>54</sup></a> Uracil derivatives can enhance the activity of antimicrobial <a href="/facts/Polysaccharide/lqXq2cJU">polysaccharides</a> such as <a href="/facts/Chitosan/BL11EEVL">chitosan</a>.<a class="footnote-ref" id="fnref:55" href="#fn:55"><sup>55</sup></a> </p><p>In <a href="/facts/Yeast/eGD24nfI">yeast</a>, uracil concentrations are inversely proportional to uracil permease.<a class="footnote-ref" id="fnref:56" href="#fn:56"><sup>56</sup></a> </p><p>Mixtures containing uracil are also commonly used to test <a href="/facts/Reversed-phase_chromatography/nc0XW7CL">reversed-phase</a> <a href="/facts/High-performance_liquid_chromatography/UNT9jPp0">HPLC</a> columns. As uracil is essentially unretained by the non-polar stationary phase, this can be used to determine the dwell time (and subsequently dwell volume, given a known flow rate) of the system. </p> <h2 id="external-links">External links</h2> <ul><li><a href="http://gmd.mpimp-golm.mpg.de/Spectrums/b3fbd853-fbf6-4ae3-aab2-e2fb5b212be3.aspx">Uracil MS Spectrum</a></li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Garrett RH, Grisham CM (1997). Principles of Biochemistry with a Human Focus. United States: Brooks/Cole Thomson Learning. <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>Behrend R (1885). "Versuche zur Synthese von Körpern der Harnsäurereihe" [Experiments on the synthesis of substances in the uric acid series]. Annalen der Chemie. 229 (1–2): 1–44. doi:10.1002/jlac.18852290102. Dasselbe stellt sich sonach als Methylderivat der Verbindung: welche ich willkürlich mit dem Namen Uracil belege, dar. [The same compound is therefore represented as the methyl derivative of the compound, which I will arbitrarily endow with the name ‘uracil’.] <a href="http://babel.hathitrust.org/cgi/pt?id=mdp.39015026321698;view=1up;seq=11" target="_blank">http://babel.hathitrust.org/cgi/pt?id=mdp.39015026321698;view=1up;seq=11</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>Ascoli A (1900). "Über ein neues Spaltungsprodukt des Hefenucleins" [On a new cleavage product of nucleic acid from yeast]. Zeitschrift für Physiologische Chemie. 31 (1–2): 161–164. doi:10.1515/bchm2.1901.31.1-2.161. Archived from the original on 12 May 2018. <a href="https://web.archive.org/web/20180512002431/https://books.google.com/books?id=SXtNAAAAYAAJ&pg=PA161" target="_blank">https://web.archive.org/web/20180512002431/https://books.google.com/books?id=SXtNAAAAYAAJ&pg=PA161</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>Brown DJ, Evans RF, Cowden WB, Fenn MD (1994). Taylor EC (ed.). The Pyrimidines. Heterocyclic Compounds. Vol. 52. New York, NY: Wiley. ISBN 9780471506560. Archived from the original on 12 May 2018. <a href="9780471506560" target="_blank">9780471506560</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Horton HR, Moran LA, Ochs RS, Rawn DJ, Scrimgeour KG (2002). Principles of Biochemistry (3rd ed.). Upper Saddle River, NJ: Prentice Hall. 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